Carboplatin and Paclitaxel or Oxaliplatin and Capecitabine With or Without Bevacizumab as First-Line Therapy in Treating Patients With Newly Diagnosed Stage II-IV or Recurrent Stage I Epithelial Ovarian or Fallopian Tube Cancer

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This randomized phase III trial studies carboplatin given together with paclitaxel with or without bevacizumab to see how well it works compared with oxaliplatin given together with capecitabine with or without bevacizumab as first-line therapy in treating patients with newly diagnosed stage II-IV, or recurrent (has come back) stage I epithelial ovarian or fallopian tube cancer. Drugs used in chemotherapy, such as carboplatin, paclitaxel, oxaliplatin, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, may block tumor growth in different ways by targeting certain cells. It is not yet known which regimen of combination chemotherapy given together with or without bevacizumab is more effective in treating epithelial ovarian cancer or fallopian tube cancer.

Patients receive carboplatin IV over 30-60 minutes on day 1 and paclitaxel IV over 3 hours on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: Carboplatin

Given IV

Other: Laboratory Biomarker Analysis

Correlative studies

Drug: Paclitaxel

Given IV

Other: Quality-of-Life Assessment

Ancillary studies

Other Name: Quality of Life Assessment

Experimental: Arm II (oxaliplatin and capecitabine)

Patients receive oxaliplatin IV over 2-6 hours on day 1 and capecitabine PO BID on days 1-14. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: Capecitabine

Given PO

Other: Laboratory Biomarker Analysis

Correlative studies

Drug: Oxaliplatin

Given IV

Other: Quality-of-Life Assessment

Ancillary studies

Other Name: Quality of Life Assessment

Experimental: Arm III (carboplatin, paclitaxel, bevacizumab)

Patients receive carboplatin and paclitaxel IV as in arm I and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-90 minutes alone on day 1. Treatment repeats every 3 weeks for 12 courses in the absence of disease progression or unacceptable toxicity.

Biological: Bevacizumab

Given IV

Drug: Carboplatin

Given IV

Other: Laboratory Biomarker Analysis

Correlative studies

Drug: Paclitaxel

Given IV

Other: Quality-of-Life Assessment

Ancillary studies

Other Name: Quality of Life Assessment

Experimental: Arm IV (oxaliplatin, capecitabine, bevacizumab)

Patients receive oxaliplatin and capecitabine as in arm II, and bevacizumab as in arm III.

Examined using Kaplan-Meier curves. The main effect size will be quantified by the hazard ratio and 95% confidence interval. Multivariate regression will also be used to examine whether there is an interaction between oxaliplatin + capecitabine and bevacizumab.

Secondary Outcome Measures
:

Incidence of adverse effects assessed by CTCAE version 4.0 [ Time Frame: Up to 7 years ]

Toxicity grades will be tabulated showing the maximum toxicity grade experienced by each patient. The proportions of patients experiencing a maximum grade of 3 or above will be compared between the treatment groups.

Progression-free survival [ Time Frame: Up to 7 years ]

Examined using Kaplan-Meier curves. The main effect size will be quantified by the hazard ratio and 95% confidence interval. Multivariate regression will also be used to examine whether there is an interaction between oxaliplatin + capecitabine and bevacizumab.

Analysis of the QOL data will use the observed scores at each time point, where available. For simplicity, the change from baseline to each of time points will be examined. However, the main analysis will be a repeated measures analysis (for example, based on a mixed model, Proc Mixed in SAS) used to simultaneously compare all QOL scores between the two treatment groups.

Response rates assessed by RECIST 1.1 [ Time Frame: Up to 7 years ]

The comparison of response rates (proportion of patients with complete and partial response, stable and progressive disease) between treatment groups, will use a chi-square test. The difference in response rates between the groups and the odds ratio (with corresponding 95% confidence intervals) will also be calculated.

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Ages Eligible for Study:

18 Years and older (Adult, Senior)

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Patients with a histologic diagnosis of mucinous adenocarcinoma of the ovary or fallopian tube with either optimal (=< 1 cm residual disease) or suboptimal residual disease following initial surgery; patients may have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or no measurable disease

All patients must have had appropriate surgery including appendectomy (unless patient has history of prior appendectomy) for ovarian or fallopian tube carcinoma with appropriate tissue available for histologic evaluation to confirm diagnosis and stage

Patients must have stage II-IV disease (new or recurrent-chemonaïve; no brain metastasis) or recurrent stage I disease (chemonaïve)

Newly diagnosed patients must begin protocol therapy within 10 weeks of primary debulking; for stage I recurrent patients (chemonaïve), they should begin protocol therapy within 14 days of randomization

Patients must have a negative colonoscopy within 1 year of enrolling in the study

Patients of childbearing potential must agree to practice an effective form of birth control during study treatment and for six months after completion of treatment

Patients who have met the pre-entry requirements

Patients must have signed an approved informed consent and authorization permitting release of personal health information

Patients with Gynecologic Oncology Group (GOG) performance grade of 0, 1 or 2

Patients with life expectancy > 3 months

Exclusion Criteria:

Patients with known colon cancer or history of colon cancer

Patients with primary peritoneal carcinoma

Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of other malignancy being present within the last 5 years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy

Patients who have received chemotherapy, radiotherapy or any investigational treatment for a gynecologic cancer (does include breast cancer) or colorectal cancer prior to enrollment

Patients with a major surgical procedure anticipated during the course of the study; this includes but is not limited to: abdominal surgery (laparotomy or laparoscopy) such as colostomy or enterostomy reversal, interval or secondary cytoreductive surgery, or second look surgery; please consult with the study chair prior to patient entry for any questions related to the classification of surgical procedures

Patients may have minor surgical procedures (i.e., mediport insertion) fine needle aspiration or core biopsies as long as it is performed > 7 days prior to the first date of bevacizumab therapy and there is no evidence of wound disruption or impaired healing

Patients with surgery (including open biopsy) within 4 weeks prior to anticipated first dose of bevacizumab (allowing for fact that bevacizumab can be omitted from first cycle of chemotherapy)

Patients with a history of abdominal fistula or perforation within the past 12 months

Patients with a current, serious, non-healing wound, ulcer, or bone fracture; patients with granulating incisions healing by secondary intention with no evidence of fascial dehiscence or infection are eligible but require weekly wound examinations

Patients with known hypersensitivity to Chinese hamster cell products or other recombinant human or humanized antibodies

Patients with mixed epithelial ovarian cancer histology

Patients with tumors of low malignant potential

History or evidence of upon physical examination of central nervous system (CNS) disease, including history of primary brain tumor or any history of brain metastases, or seizures not controlled with standard medical therapy

Uncontrolled hypertension, defined as systolic > 150 mm Hg or diastolic > 100 mm Hg; patients with a history of hypertension are permitted

Myocardial infarction or unstable angina within 12 months of the first date of bevacizumab therapy

New York Heart Association (NYHA) grade II or greater congestive heart failure or serious cardiac arrhythmia requiring medication; women who have received prior treatment with anthracycline (including doxorubicin and/or liposomal doxorubicin) and have an ejection fraction < 50% will be excluded from the study